Method for combating disturbances of the lipid content of the blood

ABSTRACT

The diethylammonium salt of hydroquinone sulfonic acid is used against disturbances of the lipid content of the blood, and against affectations stemming from such disturbancies.

United States Patent Esteve-Subirana et al. [451 Aug. 1, 1972 [54] METHOD FOR COMBATING DISTURBANCES OF THE LIPID [56] ReferencesCited [72] I ZQ ZS S I, B OTHER PUBLICATIONS nventors: n onio teveu irana arcelona, Spain; Chislain Camellia. Chem. Abst. Vol. 58 (1963) page 3332b. Bruxelles Belgium Merck Index Vol. 8 (1968) page 426.

[73] Assignees: Lahoratoires 0M, S.A., Geneva, primary Examiner sam Rosen swltzfirlandi Delalande -r Attorney-Hume, Clement, Hume and Lee bevoie, France 22 Filed: April 17,1970 ABSTRACT [21] APPL 29,683 The diethylammonium salt of hydroquinone sulfonic acid is used against disturbances of the lipid content of the blood, and against affectations stemming from [52] US. Cl ..424/3l6 Such disturbancies' [51] Int. Cl. ..A6lk 27/00 [58] 2 Claims, No Drawings Field of Search ..424/3 1 6 METHOD FOR COMBATING DISTURBANCES OF THE LIPID CONTENT OF THE BIDOD BACKGROUND OF THE INVENTION Salts of hydroquinone sulfonic acid are known to be very valuable medicaments against hemorrhagic and blood capillary diseases. It has now been found that the diethylarnmonium salt of hydroquinone sulfonic acid (having the generic name etamsylate according to the WHO list) has also a specific action on the blood lipids.

During the treatment of patients sufiering from diabetic retinitis and atheromatosis, effects were observed which could not simply be attributed to the regression of vascular fragility. Seing that atheromatosis and diabetic arteritis, in addition to their connection with vascular fragility, are influenced by other factors, such as modifications of a pathological nature of this same wall, which have been correlated to disturbances of lipid metabolism, one must consider that the two entities, which are related to disturbances of the capillary physiology, could also be advantageously modified by the administration of etamsylate.

OBJECT OF THE INVENTION Based on the clinical findings, the object of the present invention is a method for combating disturbances of the lipid content of the blood, and diseases stemming from such disturbances, comprising treating humans or animals with an eflective amount of the diethylammonium salt of hydroquinone sulfonic acid in a suitable pharmaceutical carrier.

GENERAL DESCRIPTION OF THE INVENTION The effect was first studied on laboratory animals, by subjecting them to a diet rich in cholesterol. After determining the total cholesterolemia, both free and esterified, the total lipids and the lipidogram, the animals were divided into several groups, one of these groups remaining as a reference group for the observation of the hematic concentrations of this substance. The remaining animals are used for checking the effects from the intramuscular administration of 100 mg/kg of etamsylate, the same biological parameters being measured again after two weeks treatment and dieting.

Effect of etamsylate on the lipernic picture:

Albino rabbits weighing between 1,400 g and 2,000 g were used. An analysis was made at the beginning of the test, and another after 2 weeks of feeding with food containing 1 percent cholesterol. The initial figures for the reference group are given in the following table:

Free Esteri- Total Total 1 Lipo- B Lipocholestied choles lipids propro- Ratio terol choles- -terol teins teins g terol g k mg fi/a average:

The results obtained with the reference group after 2 weeks of feeding with food containing 1 percent of cholesterol are as follows:

Initial figures for the group treated intramuscularly with 100 mg/kg of etamsylate, 6 days a week:

Free fied Total aLipo- B Lipocholescholes- -terol mg ratio g g g average:

The results obtained from the group treated intramuscularly with mg/kg of etamsylate, 6 days a week, after 2 weeks of feeding with a food containing 1 percent of cholesterol are as follows:

The previous results can be summarized in the following table:

Free &t. total total or [3 BIG ch01. chol. ch01. lipid Lip. Lip. ratio Test In group itial 0,25 0,36 0,61 661,5 33,1 66,8 2,19

afier1,53 1,30 2,83 702,8 14,7 85,3 6,2 2w. Treated Ingroup itia10,235 0,285 0,520 398,5 39 61 1,60 gfier0,626 0,736 1,362 550,4 28,2 71,8 2,70

3 SPECIFIC EMBODIMENTS OF THE INVENTION TABLE 1 Clinical test on 25 atheromatosis patients.

Administration of 750 mg etamsylate (3 tablets of 250 mg per day). Duration of treatment: 30 days Before After Before After cholestcholesterlipoproteins lipoproteins case erolemia olernia no totestoesa B pl a ,8 Bio:

tal ter. tal ter.

ues

STATISTICAL ANALYSIS OF TABLE 1 Average values platelets significant Bleeding 3.36 2.35 6.0 very time significant (p 0.00 l Fragility 33.8 7.6 10.0 very index significant (p 0.001) Total esterified blood chloesterol 58.7 62.1 2.6 significant due to the (p 0.025) ester increase after treatment Lipoprotein 4.92 4.04 3.0 significant mainly due to B/a ratio (p 0.01) then; increase after treatment Oral administration of 750 mg of ETAMSYLATE for 25-60 days Patients suffering from dyslipidemia without abnormal capillary fragility Dura- Chlo- Esterif- No [nit Ageof estrol ratio Lipoprotein ratio treat beat'- beaf- -rnent fore ter fore ter before after 1 PG 50 40 345 222 60 90l10=9 l20=4 days days

days

5 BC 64 45 324 280 60 7180/20=4 77l23=3.3

days

6 CL 39 60 260 225 51 75 82/18=4.5 75l25=3 days 7 PG 41 50 282 2,5 72 80 89lll=8l1 79/21=3.7

8 SM 38 55 258 206 56 83 84/16=5.2 7S/25=3 TABLES Arterio-sclerosis or diabetic patients with important alterations of the lipidogram ETAMSYLATE: 750 mg orally for 1 month Rapport Total Esteriof Total lipids lipoproteins cholesfied cholesteriinit mg [3A ratio terol esterol fication beaf-beafbeaf before alter before after fore terfore ter fore ter RT 825 1025 5.25 4.90 240 218100 41 60 DV 3.15 2.45 167 200 70 81 42 41 LM 805 735 3.40 3 178 180 74 80 41 44 PF 770 675 4.70 4.10 256 230108 104 42 45 MC 1040 895 4.10 4 308 280153 139 50 50 MG 770 595 3.85 3.90 194 220 90 104 46 47 AE 1780 1260 5.35 4.80 285 275132 46 53 Treatment: 3 tablets per day for one month TABLE 4 Arterio-sclerosis or diabetic patients with important alterations of the lipidogram ETAMSYLATE: 750 mg orally for 1 month Treatment: 3 tablets per day for one month of the blood the process which comprises, treating humans and animals in need of such modification by the steps of administering thereto the diethylammonium salt of hydroquinone sulfonic acid in a suitable pharmaceutical carrier and in amounts and for a time sufficient to decrease the lipoprotein fl/a ratio of the blood.

2. A method for reducing the cholesterol content of the blood which comprises, treating humans and animals having abnormally high amounts of blood cholesterol by administering thereto the diethylammonium salt of hydroquinone sulfonic acid in a suitable pharmaceutical carrier in amounts and for a time sufficient to reduce the cholesterol blood level. 

2. A method for reducing the cholesterol content of the blood which comprises, treating humans and animals having abnormally high amounts of blood cholesterol by administering thereto the diethylammonium salt of hydroquinone sulfonic acid in a suitable pharmaceutical carrier in amounts and for a time sufficient to reduce the cholesterol blood level. 